Natural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16 ؉ NK cells predominated in peripheral blood, whereas most mucosal NK cells were CD56 ؉ , and lymph nodes contained both CD56 ؉ and CD16 ؊ CD56 ؊ (doublenegative [DN]) subsets. Functional profiles were also distinct among subsets-CD16 ؉ NK cells expressed high levels of cytolytic molecules, and CD56 ؉ NK cells were predominantly cytokine-secreting cells, whereas DN NK possessed both functions. In macaques chronically infected with SIV, circulating CD16 ؉ and DN NK cells were expanded in number and, although markers of cytoxicity increased, cytokine secretion decreased. Notably, CD56 ؉ NK cells in SIV-infected animals up-regulated perforin, granzyme B, and CD107a. In contrast, the lymph nodehoming molecules CD62 ligand (CD62L) and C-C chemokine receptor type 7 (CCR7), which are expressed primarily on CD56 ؉ and DN NK cells, were significantly down-regulated on NK cells from infected animals. These data demonstrate that SIV infection drives a shift in NK-cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs, suggesting that the NK-cell repertoire is not only heterogeneous but also plastic. IntroductionSince their discovery in the 1970s, natural killer (NK) cells have been considered the major effector cells of the innate immune system because of their ability to kill virus-infected or neoplastic cells. Although NK cell-mediated killing does not require prior antigen sensitization, cell-to-cell contact between NK and target T cells occurs through a complex array of inhibitory and activating receptors. In humans, NK cells express both killer-cell immunoglobulin-like receptors (KIRs), which interact with major histocompatibility complex (MHC) class I molecules and can be either inhibitory or activating, and receptors belonging to the C-type lectin family such as natural killer group 2A (NKG2A), an inhibitory receptor that recognizes HLA-E and NKG2D, which recognizes the stress-induced ligands MHC class I chain-related gene A and B (MICA/MICB) and members of the ULBP family. 1 Human NK cells also express various natural cytotoxicity receptors including NKp46, NKp30, and NKp44, for which the ligands remain incompletely characterized. 2,3 However, increasing evidence suggests that the complexity of NK-cell function has been underappreciated and that in addition to cytolysis of aberrant T cells, NK cells also produce a wide array of cytokines, mediate tolerance to self-antigens, and regulate dendritic cell functions. 4 Most recently, murine studies have suggested that NK cells may even display characteristics of adaptive immune responses. 5 In humans, 2 primary phenotypically defined subsets of NK cells have been described, cytolytic CD56 dim CD16 ϩ and cytokinesecreting CD56 bright CD16 Ϫ subsets, of which the CD56 dim CD16 ϩ subset predomina...

Background: During the coronavirus disease (COVID-19) pandemic, harsh social distancing measures were taken in China to contain viral spread. We examined their impact on the lives of medical students. Methods: A nation-wide cross-sectional survey of college students was conducted from 4–12 February 2020. We enrolled medical students studying public health in Beijing and Wuhan to assess their COVID-19 awareness and to evaluate their mental health status/behaviors using a self-administered questionnaire. We used the Patient Generalized Anxiety Disorder-7 and Health Questionnaire-9 to measure anxiety disorders and depression. We used multivariable logistic regression and path analysis to assess the associations between covariates and anxiety disorder/depression. Results: Of 933 students, 898 (96.2%) reported wearing masks frequently when going out, 723 (77.5%) reported daily handwashing with soap, 676 (72.5%) washed hands immediately after arriving home, and 914 (98.0%) reported staying home as much as possible. Prevalence of anxiety disorder was 17.1% and depression was 25.3%. Multivariable logistic regression showed anxiety to be associated with graduate student status (odds ratio (aOR) = 2.0; 95% confidence interval (CI): 1.2–3.5), negative thoughts or actions (aOR = 1.6; 95% CI: 1.4–1.7), and feeling depressed (aOR = 6.8; 95% CI: 4.0–11.7). Beijing students were significantly less likely to have anxiety than those in the Wuhan epicenter (aOR = 0.9; 95% CI: 0.8–1.0), but depression did not differ. Depression was associated with female students (aOR = 2.0; 95% CI: 1.2–3.3), negative thoughts or actions (aOR = 1.7; 95% CI: 1.5–1.9), and anxiety disorder (aOR = 5.8; 95% CI: 3.4–9.9). Path analysis validated these same predictors. Conclusions: Despite medical students’ knowledge of disease control and prevention, their lives were greatly affected by social distancing, especially in the Wuhan epicenter. Even well-informed students needed psychological support during these extraordinarily stressful times.

ObjectivePre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.DesignWe performed a case–control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.ResultsPatients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased.ConclusionsThis study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

BACKGROUND: Patients with cancer have a higher risk of coronavirus disease 2019 (COVID-19) than noncancer patients. The authors conducted a multicenter retrospective study to investigate the clinical manifestations and outcomes of patients with cancer who are diagnosed with COVID-19. METHODS: The authors reviewed the medical records of hospitalized patients who were treated at 5 hospitals in Wuhan City, China, between January 5 and March 18, 2020. Clinical parameters relating to cancer history (type and treatment) and COVID-19 were collected. The primary outcome was overall survival (OS). Secondary analyses were the association between clinical factors and severe COVID-19 and OS. RESULTS: A total of 107 patients with cancer were diagnosed with COVID-19, with a median age of 66 years (range, 37-98 years). Lung (21 patients; 19.6%), gastrointestinal (20 patients; 18.7%), and genitourinary (20 patients; 18.7%) cancers were the most common cancer diagnoses. A total of 37 patients (34.6%) were receiving active anticancer treatment when diagnosed with COVID-19, whereas 70 patients (65.4%) were on follow-up. Overall, 52.3% of patients (56 patients) developed severe COVID-19; this rate was found to be higher among patients receiving anticancer treatment than those on follow-up (64.9% vs 45.7%), which corresponded to an inferior OS in the former subgroup of patients (hazard ratio, 3.365; 95% CI, 1.455-7.782 [P = .005]). The detrimental effect of anticancer treatment on OS was found to be independent of exposure to systemic therapy (case fatality rate of 33.3% [systemic therapy] vs 43.8% [nonsystemic therapy]). CONCLUSIONS: The results of the current study demonstrated that >50.0% of infected patients with cancer are susceptible to severe COVID-19. This risk is aggravated by simultaneous anticancer treatment and portends for a worse survival, despite treatment for COVID-19. Cancer 2020;126:4023-4031.